Lymphoma is the third most common cancer among children in the world. The major types of lymphoma are Hodgkin's and non-Hodgkin's. Non-Hodgkin's lymphoma (NHL) occurs more frequently than Hodgkin's disease among children. The major histopathological categories of NHL in children are (1) Burkitt's and Burkitt's like lymphomas; (2) lymphoblastic lymphomas; (3) anaplastic large cell lymphoma; and (4) diffuse large cell lymphomas (Percy et al., 1999). In recent years, much progress has been made toward understanding the molecular and cellular biology of NHL. Many important contributions have been made by the characteristics of chromosal translocations and identification of several key genetic factors associated with each type of NHL (Percy et al., 1999). However, the treatments of NHL still mainly depend on chemotherapy and radiotherapy. This is because the molecular mechanisms underlying the pathogenesis of NHL remain largely unclear.
Lymphoblastic lymphoma, a predominant T-cell tumor, accounts for about 30% of childhood NHL (National Cancer Institute Cancer.gov Web site, 2004). Recent studies have shown that T cell lymphoblastic lymphoma is caused by abnormal expression of several genetic factors such as BCL-6 (Hyjek et al., (2001) Blood. 97: 270–276), MSH2/Lmo-2Tal-1 (Lowsky et al., (1997) Blood. 89: 2276–2282) and Stat5 (Kelly et al., (2003) J Exp Med. 198: 79–89). Stat5 has been shown to play a role in cell cycle regulation (Nieborowska-Skorska et al., (1999) J Exp Med. 189: 1229–1242; Martino et al., (2001) J Immunol. 166: 1723–1729). Therefore, future strategies for the prevention and treatment of T cell lymphoblastic lymphoma will focus on the elucidation of genetic substances associated with cell cycle regulation. Interestingly, three members (RSK1, RSK2, and RSK3) of the ribosomal S6 kinase (RSK) family have been shown to be involved in the cell cycle regulation and may play a role in T cell (Edelmann et al., (1996) J Biol chem. 271: 963–71; Zhao et al., (1996) J Biol Chem. 271: 29773–29779; Brennan et al., (1999) Mol Cell Biol. 19:4729–38; Suzuki et al., (2001) J Immunol. 167:3064–73). Thus, it raised a possibility that RPS6KA6 (ribosomal S6 kinase 4; also named RSK4; GenBank accession # AF184965) has a role in the development of T cell lymphoblastic lymphoma. Therefore, the discovery of gene variants of RPS6KA6 may be important targets for diagnostic markers of T cell lymphoblastic lymphoma.